Moringa oleifera and Its Phytochemicals Targeting Parkinson's Disease: Insights from Network Pharmacology

Introduction: Moringa oleifera, known as the "miracle tree," is a medicinal plant rich in bioactive phytochemicals with notable antioxidant, anti-inflammatory, and neuroprotective properties. These compounds hold strong potential as a multi-target therapeutic strategy for Parkinson’s disease (PD), a neurodegenerative disorder characterized by oxidative stress, neuroinflammation, and loss of dopaminergic neurons.
Methods: Phytochemicals from M. oleifera leaves were retrieved from IMPPAT and Dr. Duke’s databases. Nine lead compounds were selected after evaluation of drug-likeness (Lipinski’s Rule of Five), ADME properties, toxicity profiles, and blood-brain barrier permeability. Potential targets were predicted using SwissTargetPrediction and SuperPred, and 64 overlapping genes with PD-related genes from GeneCards were identified. Protein-protein interaction (PPI) networks were constructed in Cytoscape, hub genes were ranked using CytoHubba, and GO/KEGG pathway enrichment was performed with g:Profiler. A drug-protein-pathway network was built, followed by molecular docking (AutoDock Vina/PyRx). Molecular dynamics (MD) simulation and DFT analysis, including HOMO-LUMO calculations, were performed on the lead phytochemicals.
Results: Network analysis highlighted key hub genes and significant enrichment in oxidative stress, MAPK, PI3K-Akt, apoptosis, and neuroinflammatory pathways. Molecular docking showed favorable binding affinities, while MD simulation and DFT (HOMO-LUMO) analysis of the lead compounds confirmed their stability and reactivity profiles supportive of therapeutic potential.
Conclusions: This comprehensive network pharmacology study combined with molecular docking, MD simulation, and DFT analysis provides valuable insights into the multi-target mechanisms of M. oleifera phytochemicals against PD. The findings offer a strong basis for further experimental validation and development of natural product-based interventions for Parkinson’s disease.